To investigate the effects of genetic and environmental factors, and their interactions, on respiratory health in adults we have established several high-quality population resources. We have been working with the extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study to examine both genetic and environmental factors in adult respiratory health. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We added the assessment of exposure to traffic to this dataset and have examined this surrogate of traffic related air pollution in relation to respiratory and cardiovascular endpoints. We found that higher exposure to traffic was related to lower pulmonary function (Kan et al, 2007 - reported in previous annual report) and myocardial infarction (Kan et al, 2008). We have also found that higher dietary fiber was related to better pulmonary function, a results consistent with our earlier finding in the Singapore Chinese Health Study. In the past year, we have doing analyzing pulmonary function in relation to genome wide association genotyping in ARIC. The genotyping data were made available with funding from other NIH agencies. Samples on the entire cohort were genotyped with the 1 million SNP Affymetrix platform. Through the analysis of the ARIC data, we formed a pulmonary function analysis group within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology) which includes several other cohorts with genome wide association genotyping and pulmonary function data. We have been doing meta-analysis of genome wide association results with three other CHARGE cohorts the Framingham Heart Study, the Cardiovascular Health Study, and the Rotterdam Study. We found several novel loci related to pulmonary function and replicated most of these in a second consortium called SpiroMeta. These results are under review. In the next fiscal year, we also plan to examine genome wide interactions with environmental factors including smoking, traffic related air pollution, and dietary factors that we found to be related to pulmonary function in ARIC. Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We continued to expand these observations in new papers this year. To follow-up on these observations, we have bugen a new study which is described in a separate annual report - ES102385-01. Another population is the NIEHS Sister Study. This NIEHS cohort has enrolled 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is being followed up annually. In collaboration with investigators at the EPA-UNC Human Exposure Facility, I have established a study to follow-up on recent experimental work showing that obese mice have greater respiratory response to ozone than lean mice. This work also follows up our recent finding that subjects with higher BMI have greater drop in pulmonary function (FEV1) in response to acute ozone exposure(Bennett et al., Inhalation Toxicology, 2007). We have established an experimental study where we expose centrally obese and lean women to ozone and measure spirometry, air resistance, airway hyperresonsiveness and inflammatory responses to the exposure. Enrollment is approximately 50% complete for this study.